Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population

Aleksey G Nikitin; Viktor Y Potapov; Olga I Brovkina; Ekaterina O Koksharova; Dmitry S Khodyrev; Yury I Philippov; Marina S Michurova; Minara S Shamkhalova; Olga K Vikulova; Svetlana A Smetanina; Lyudmila A Suplotova; Irina V Kononenko; Viktor Y Kalashnikov; Olga M Smirnova; Alexander Y Mayorov; Valery V Nosikov; Alexander V Averyanov; Marina V Shestakova

doi:10.7717/peerj.3414

Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population

PeerJ. 2017 Jul 13:5:e3414. doi: 10.7717/peerj.3414. eCollection 2017.

Authors

Aleksey G Nikitin^#¹, Viktor Y Potapov^#², Olga I Brovkina^#¹, Ekaterina O Koksharova^#³, Dmitry S Khodyrev^#¹, Yury I Philippov^#³, Marina S Michurova^#³, Minara S Shamkhalova^#³, Olga K Vikulova^#^{3

4}, Svetlana A Smetanina^#⁵, Lyudmila A Suplotova^#⁵, Irina V Kononenko^#^{3

4}, Viktor Y Kalashnikov^#³, Olga M Smirnova^#^{3

4}, Alexander Y Mayorov^#^{3

4}, Valery V Nosikov^#⁶, Alexander V Averyanov^#¹, Marina V Shestakova^#^{3

4}

Affiliations

¹ Federal Research Clinical Center for Specialized Types of Health Care and Medical Technologies of Federal Medical and Biology Agency, Moscow, Russian Federation.
² Clinic of New Medical Technologies "Archimedes", Moscow, Russian Federation.
³ Endocrinology Research Centre, Moscow, Russian Federation.
⁴ I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.
⁵ Tyumen State Medical University, Tyumen, Russian Federation.
⁶ State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, Russian Federation.

^# Contributed equally.

Abstract

Background: The association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes.

Methods: The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-β were used to measure insulin resistance and β-cell secretory function, respectively.

Results: The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired β-cell function.

Conclusion: In the Russian population, genes, which affect insulin synthesis and secretion in the β-cells of the pancreas, play a central role in the development of T2DM.

Keywords: Genetic predisposition; Polymorphic marker; Type 2 diabetes mellitus.

Grants and funding

The research was supported by the Russian Science Foundation (No. 14-25-00181). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.